It has been hypothesized that extinction of conditioned fear leads to the formation of a new memory, but little is known about the neural mechanisms. Previous studies have reported that N-methyl-D-aspartate (NMDA) receptors are necessary for extinction memory. We have shown that a systemic NMDA antagonist has no effect on short-term extinction memory, but blocks recall of extinction 24-hours later, suggesting a role of NMDA receptors in consolidation of extinction learning. NMDA mediated calcium entry and its molecular sequelae (including protein synthesis) might be necessary for long-term extinction memory. in a parallel finding, a lesion of the ventro-medial prefrontal cortex (VmPFC) blocks long-term, but not short-term extinction memory, implicating this brain structure in consolidation of extinction. Specific aim 1: We will determine if long-term extinction memory requires protein synthesis. Hypothesis: Intra-ventricular infusion of the protein synthesis inhibitor anisomycin during extinction training will spare short-term extinction memory, but will prevent 24-hour recall of extinction. Specific aim 2: We will determine if the effects of NMDA blockade and protein synthesis inhibitors on fear extinction are mediated via the vmPFC. Hypothesis: Micro-infusions of the NMDA receptor antagonist AP5 and anisomycin into the vmPFC will block long-term but not short-term extinction memory. Specific aim 3: We will determine the molecular pathways that connect NMDA activation and protein synthesis in the vmPFC during extinction of auditory fear conditioning. Hypothesis: Microinfusions of the mitogen-activated protein kinase (MAPK) inhibitor PD98059 into the vmPFC will block long-term but not short-term extinction memory. Understanding the molecular mechanisms of extinction consolidation could lead to new treatments for anxiety disorders.